We are conducting a multidisciplinary study of biochemical, physiologic, and pathologic sequences involved in acute lung injury and repair. The major clinical and laboratory foci are: elucidating the initial causes and effects of pulmonary vascular injury during severe ARDS by using hemodynamic and angiographic studies as well as quantitation of light microscopy and ultrastructural analysis, investigating connective tissue metabolism focusing on injured lung cell biology, studying the interaction of platelets and the coagulation system with the acutely injured lung, and learning if prostanoid metabolites such as thromboxanes mediate lung injury. We are examining the nature and role in acute lung injury of pulmonary thrombosis and vasospasm as causes of vascular obstruction in acute respiratory failure of diverse etiology. We are assessing the function of the right ventricle during clinical ARDS by scintillation scanning and thermodilution. We are defining the response of the lung to oxygen breathing in lymph fistula sheep and rats and alteration of injury by antifibrotic (L3, 4 dehydroproline) and antioxidant (Vitamin E) drugs. Since it may be central to several mechanisms, we are investigating prostanoid metabolism by using high performance liquid chromatography and radioimmunoassay. We are assessing the production of prostacyclin and thromboxanes in animals and ARDS patients. Membrane lung bypass is being used to assist study of the effects of reduced pulmonary blood flow on the pulmonary metabolism of prostanoids and interstitial fluid (lymph) formation.